Dyslipidemia is a large risk factor of arteriosclerosis, and arteriosclerosis is the cause of coronary artery diseases such as angina pectoris and myocardial infarction and cerebral stroke such as cerebral hemorrhage and cerebral infarction which are major death causes of Japanese. In the meanwhile, it has been demonstrated that these cardiovascular diseases can be prevented and treated by treating such dyslipidemia.
According to the diagnostic criteria of Atherosclerotic Diseases Prevention Guideline (2012), dyslipidemia is divided into hyper-LDL cholesterolemia (LDL cholesterol (hereinafter also referred to as “LDL-C”) 140 mg/dL), borderline hyper-LDL-cholesterolemia (LDL-C, 120 to 139 mg/dL), low HDL cholesterolemia (HDL cholesterol (hereinafter also referred to as “HDL-C”)<40 mg/dL), and hypertriglyceridemia (triglyceride (hereinafter also referred to as “TG”)≧150 mg/dL). Recently, the hyper-LDL cholesterolemia, the low HDL-cholesterolemia, and the hypertriglyceridemia are conceived as independent risk factors.
The therapeutic agent used for the dyslipidemia differs by the type of the dyslipidemia, and statin is the first choice for treating the hyper-LDL-cholesterolemia. Statin acts in mevalonic acid synthetic pathway wherein biosynthesis of isopentenyl diphosphoric acid and dimethyl allyl diphosphoric acid (starting materials of steroid synthesis) from acetyl CoA takes place by inhibiting HMG-CoA reductase (EC 1.1.1.34) (hereinafter also referred to as “HMG-CoA”) which is an enzyme catalyzing the reaction of reducing hydroxymethyl glutaryl CoA to mevalonic acid, and thereby suppressing the biosynthesis of the cholesterol. The thus reduced cholesterol biosynthesis also invites effects such as enhanced expression of liver LDL (low density lipoprotein) receptor, increased incorporation of LDL-C from the blood into the liver, suppressed VLDL (very low density lipoprotein) secretion into the blood, and reduced serum TG and increased HDL-C. In view of such function of the statin, statin is also referred to as HMG-CoA reductase inhibitor (HMG-CoA RI).
Statin is effective for the treatment of cardiovascular diseases and prevention of cardiovascular events, and statin has been considered to be a safe drug with high tolerability. However, recent reports indicate relation between the statin and the risk of diabetes incidence. For example, Non-Patent Document 1 discloses that, in the general evaluation conducted by collecting the results of 16 clinical trials wherein participants were divided into the group administered with statin (lipid lowering drug) and the group not administered with the statin, the risk of diabetes incidence was 9% higher in the group administered with the statin. In addition, United States Food and Drug Administration announced a safety communication on the increase of blood glucose and risk of type 2 diabetes incidence by the statin administration in February, 2012, and the package insert of the statin preparation now includes the description that the statin administration invited an increase of hemoglobin Alc (hereinafter also referred to as “HbAlc”) and fasting blood glucose and significant increase in the diabetes incidence (Non-Patent Document 2). However, it has been conceived, even if the risk of diabetes incidence should increase by the statin administration, the benefit of the reduced risk of the cardiovascular event incidence by the statin exceeds such risk and there is no reason for stopping the statin administration. On the other hand, it has also been conceived that the statin should be used with the monitoring of the blood glucose and the glycohemoglobin blood glucose in the case of patients with borderline blood glucose and the like suffering from high risk of diabetes incidence (Non-Patent Document 3).
Some reports examine relation between the type of statin and the risk of the diabetes incidence. For example, Non-Patent Document 4 evaluated new incidence of the diabetes in aged people of at least 66 years old administered with statin, and reports that the risk of the incidence of the diabetes significantly increased in the case of atorvastatin, rosuvastatin, and simvastatin compared to the case of pravastatin, and no significant difference was found in the case of fluvastatin and lovastatin. Non-Patent Document 5 describes that, in the meta-analysis of the tolerability and safety of the statin, the risk of the incidence of the diabetes increased by the statin administration while no difference was found by the type of the statin.